title: Selective regulation of MAP kinase signaling by an endomembrane phosphatidylinositol 4-kinase.
abstract: Multiple MAP kinase pathways share components yet initiate distinct biological processes. Signaling fidelity can be maintained by scaffold proteins and restriction of signaling complexes to discreet subcellular locations. For example, the yeast MAP kinase scaffold Ste5 binds to phospholipids produced at the plasma membrane and promotes selective MAP kinase activation. Here we show that Pik1, a phosphatidylinositol 4-kinase that localizes primarily to the Golgi, also regulates MAP kinase specificity but does so independently of Ste5. Pik1 is required for full activation of the MAP kinases Fus3 and Hog1 and represses activation of Kss1. Further, we show by genetic epistasis analysis that Pik1 likely regulates Ste11 and Ste50, components shared by all three MAP kinase pathways, through their interaction with the scaffold protein Opy2. These findings reveal a new regulator of signaling specificity functioning at endomembranes rather than at the plasma membrane.
authors.affiliation: Department of Pharmacology, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
authors.forename: Steven D
authors.initials: SD
authors.lastname: Cappell
authors.forename: Henrik G
authors.initials: HG
authors.lastname: Dohlman
mesh_terms: D019870:1-Phosphatidylinositol 4-Kinase / Q000502:physiology*; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D004843:Epistasis, Genetic; D005656:Fungal Proteins / Q000378:metabolism; D007425:Intracellular Membranes / Q000737:chemistry*; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism; D020935:MAP Kinase Signaling System; D008565:Membrane Proteins / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D005656:Fungal Proteins; D008565:Membrane Proteins; C547524:Opy2 protein, S cerevisiae; C080321:STE5 protein, S cerevisiae; C079506:STE50 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D019870:1-Phosphatidylinositol 4-Kinase; D020930:MAP Kinase Kinase Kinases; C067018:Ste11 protein, S cerevisiae